TLR agonists regulate PDGF-B production and cell proliferation through TGF-β/type I IFN crosstalk

Edward K. Chow, Ryan M. O'Connell, Stephen Schilling, Xiao Fan Wang, Xin Yuan Fu, Genhong Cheng

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Transforming growth factor-β (TGF-β) and type I interferon (IFN) autocrine/paracrine loops are recognized as key mediators of signaling cascades that control a variety of cellular functions. Here, we describe a novel mechanism by which Toll-like receptor (TLR) agonists utilize these two autocrine/paracrine loops to differentially regulate the induction of PDGF-B, a growth factor implicated in a number of diseases ranging from tumor metastasis to glomerulonephritis. We demonstrate that CpG-specific induction of PDGF-B requires activation of Smads through TGFβ1 autocrine/paracrine signaling. In contrast, polyinosinic:polycytidylic acid strongly represses CpG's as well as its own intrinsic ability to induce PDGF-B mRNA through type I IFN-mediated induction of Smad7, a negative regulator of Smad3/4. Furthermore, we have shown that this crosstalk mechanism translates into similar regulation of mesangial cell proliferation. Thus, our results demonstrate the importance of crosstalk between TGF-β and type I IFNs in determining the specificity of TLR-mediated gene induction.

Original languageEnglish
Pages (from-to)4071-4081
Number of pages11
JournalEMBO Journal
Volume24
Issue number23
DOIs
StatePublished - Dec 7 2005

Fingerprint

Interferon Type I
Toll-Like Receptors
Cell proliferation
Transforming Growth Factors
Crosstalk
Autocrine Communication
Cell Proliferation
Paracrine Communication
Poly I-C
Mesangial Cells
Glomerulonephritis
Tumors
Intercellular Signaling Peptides and Proteins
Genes
Chemical activation
Neoplasm Metastasis
Messenger RNA
Neoplasms

Keywords

  • PDGF-B
  • Proliferation
  • TGF-β
  • Toll-like receptors
  • Type I interferons

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Chow, E. K., O'Connell, R. M., Schilling, S., Wang, X. F., Fu, X. Y., & Cheng, G. (2005). TLR agonists regulate PDGF-B production and cell proliferation through TGF-β/type I IFN crosstalk. EMBO Journal, 24(23), 4071-4081. https://doi.org/10.1038/sj.emboj.7600867

TLR agonists regulate PDGF-B production and cell proliferation through TGF-β/type I IFN crosstalk. / Chow, Edward K.; O'Connell, Ryan M.; Schilling, Stephen; Wang, Xiao Fan; Fu, Xin Yuan; Cheng, Genhong.

In: EMBO Journal, Vol. 24, No. 23, 07.12.2005, p. 4071-4081.

Research output: Contribution to journalArticle

Chow, EK, O'Connell, RM, Schilling, S, Wang, XF, Fu, XY & Cheng, G 2005, 'TLR agonists regulate PDGF-B production and cell proliferation through TGF-β/type I IFN crosstalk', EMBO Journal, vol. 24, no. 23, pp. 4071-4081. https://doi.org/10.1038/sj.emboj.7600867
Chow, Edward K. ; O'Connell, Ryan M. ; Schilling, Stephen ; Wang, Xiao Fan ; Fu, Xin Yuan ; Cheng, Genhong. / TLR agonists regulate PDGF-B production and cell proliferation through TGF-β/type I IFN crosstalk. In: EMBO Journal. 2005 ; Vol. 24, No. 23. pp. 4071-4081.
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